The overall aim of these studies is to design and utilize a fetal/neonatal macaque model for the evaluation of the potential toxicities of various anti-HIV drug treatment(s) proposed for use in the human pediatric patient. Our long-term objectives will be (1) to devise methods for assessing potential pre- and postnatal toxicities during exposure to anti-HIV drug therapies, (2) to evaluate various drug treatment and administration periods for testing the potential toxicities of various anti-HIV drugs, (3) to determine the effects of pre- and postnatal anti-HIV treatment strategies on normative growth and development, specifically related to neurobehavioral, hematologic, and physiologic parameters, and (4) to correlate adverse effects with drug levels achieved in the maternal, fetal, and neonatal/infant compartments. One of the greatest challenges with new anti-HIV therapies will be to determine the route of administration and dosages to be used. Within Specific Aim 1, we will establish methods for treating the drug(s) under scrutiny. Drug administration via the maternal (oral or intravenous [IV]), fetal ("oral" via amniotic fluid, intraperitoneal, or IV), and neonatal/infant (oral, IV) routes will be evaluated using AZT as a prototype drug. In addition to monitoring for toxicity, these studies will provide information on drug levels achieved in various maternal (serum, urine), fetal (amniotic fluid, serum, cerebrospinal fluid [CSF]), and neonatal (serum, urine, CSF) compartments. The information gained from these studies will be applied to further evaluations of the potential toxic and adverse effects of prenatal and pre- and postnatal treatment of various anti-HIV drugs by monitoring growth and neurobehavioral development (Specific Aim 2) and hematologic effects while monitoring drug levels achieved in various maternal, fetal, and neonatal/infant compartments (Specific Aim 3). Both treatment periods (prenatal [gestational day (GD) 60-160] and pre-and postnatal [GD 60-160 and daily for 6 months]) will be pursued since it is currently unknown if pre- and postnatal treatment alone will prove sufficient to alter transmission of the virus or the course of infection. It will be important to identify the spectrum of adverse effects that may be related to this lengthy exposure period. With the studies outlined above we will be able to compare the differing routes of drug administration (maternal versus fetal) in addition to a varying length of drug exposure (prenatal versus pre- and postnatal). It is our goal to evaluate the optimal methods for drug delivery while minimizing toxic or adverse effects, and to determine the potential ramifications or various drug treatment strategies on pre-and postnatal individuals.